Optimization of Cervical Cancer Screening Among Women Living With HIV in Latin American Countries
NCT ID: NCT06002126
Last Updated: 2025-11-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
NA
1002 participants
INTERVENTIONAL
2023-08-02
2027-03-31
Brief Summary
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Women living with HIV (WLWH) in this study will be seen once, twice or three times in a year. Women will provide several samples related to screening for cervical cancer including a swab of the cervix, a self-collected swab of the vagina and urine. Women will have a detailed examination of the cervix called colposcopy and have a few biopsies, or small pinches of the cervix, to look for areas at risk for turning into cancer. If HPV of the cervix is found but treatment of the cervix is not indicated, women will return in 6 months and in 12 months to repeat these tests. Most women will only need 1 visit. Women found to have damaged areas of the cervix at risk for turning into cancer will be referred for treatment.
This protocol will compare different tests to understand the best test to identify women at risk for cervical cancer.
Detailed Description
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The hypotheses for this protocol includes:
• The Xpert HPV test can be optimized for HSIL detection (CIN2+) in WLWH to significantly improve test specificity, when compared to unmodified test output using manufacturer guidelines.
To evaluate this hypothesis, we will enroll 1000 women aged 25-65 years living with HIV who are undergoing routine cervical cancer screening. These individuals will be recruited from affiliated clinical sites of the Instituto Nacional de Salud Pública in Cuernavaca, Mexico and Universidade de São Paulo in São Paulo, Brazil. Participants will provide a first void urine sample and will be instructed how to self-collect a vaginal swab. An oral gargle specimen will be collected for HPV testing, host DNA methylation, and Epstein-Bar Virus (EBV) co-infection. They will receive a baseline questionnaire about risk factors for HPV and cervical cancer, and provide blood specimens for cluster of differentiation 4/8 (CD4/CD8) count, plasma viral load, as well as future DNA methylation of biological aging and circulating tumor HPV DNA (ctHPVDNA) analysis, and stored sera. Next, a provider will collect an anal swab. Then the participant will undergo a speculum exam, and a provider will collect a cervical cytobroom sample for cytology and HPV testing followed by a swab for stored specimens. Then at least two cervical biopsies will be obtained.
Material from one provider-collected cervical swab will undergo cervical cytology assessment using Bethesda Criteria. Cervical histology results from the collected biopsies will be interpretated according to the Lower Anogenital Squamous Terminology (LAST). HSIL will be defined as CIN 2 with diffuse p16 staining, CIN 2-3, or CIN 3. Women diagnosed with HSIL will be treated according to local standards. The local histology result will be used for the management of participants. Any lesions suspicious for invasive cancer will be referred to the appropriate specialist. Women with HSIL on cytology, but no HSIL on histology will be treated according to the local standard. The management options include repeat colposcopy, endocervical curettage, or a diagnostic loop electro-excision procedure. Similarly, women with a Type 3 transformation zone should have endocervical curettage and be managed according to local standards. After local pathology review, all histology specimens will be shipped centrally for Histology Endpoint Adjudication; these adjudicated histology results will be used for reporting research findings. Discordance between the local and central pathology review will be adjudicated with a second central pathologist. The final histology result will be sent back to the local site and provided to the participant and their providers. Women found to have vulvar, vaginal or perianal lesions suspicious for HSIL will be referred for appropriate evaluation.
The self-collected vaginal swab and material from the provider-collected cytobroom sample will be tested for HPV using Xpert HPV. Xpert testing of self- and provider-collected samples will be conducted locally (at the point of care) in Brazil and Mexico. Remaining material from the vaginal and cervical samples will be shipped to Dr. Villa's lab in Brazil to allow for Qiagen' methylation testing of any WLWH with hrHPV detected. Residual samples, as well as the collected urine, will be stored in Dr. Villa's lab for future studies. In addition, an optional collection of anal canal and a cervical swab will occur in those that specifically provided consent. These specimens will be stored for future medical research and will not be analyzed as part of this study.
Women with hrHPV detected on a provider-collected cervical sample using a locally available and approved test, but who were negative for HSIL as determined by cervical biopsy, will be asked to return for a follow-up study visit at 6-month to receive the same procedures described above (with the exception of blood draws). If at the 6-month follow-up visit WLWH continue to have detection of hrHPV, but are HSIL-negative by biopsy, they will be asked to return for an additional follow-up study visit 6 months later (12-months post-baseline) to receive the same procedures (with blood draws). We estimate that approximately 40% of the population will have hrHPV detected and may need to return for a follow-up visit; and 7% will be HSIL+ and referred for treatment.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
DIAGNOSTIC
NONE
Study Groups
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Cervical cancer screening (single arm)
Women will be screened for cervical cancer with HPV testing that provides extended genotyping and DNA quantification. Women will also provide other samples for cervical cancer screening tests. Women will under cervical biopsies.
Xpert HPV
The Cepheid Xpert HPV Assay (Xpert HPV) is a qualitative, real-time polymerase chain reaction (PCR) assay for the detection of hrHPV DNA. The assay is formatted in a single-use, Xpert HPV test cartridge and is run on the Cepheid Xpert® System, a multi-analyte, random access, molecular-diagnostic platform ranging in capacity from 1 to 80 test processing modules. Importantly, a single hrHPV DNA test can be completed in one hour, permitting same-day screening and diagnosis (e.g. colposcopy) or treatment (e.g. cryotherapy), reducing the potential for loss to follow-up in lower-resource settings. It uses liquid-based cytologic media and yields five separate results or channels: HPV 16, HPV 18/45, HPV 31/33/35/52/58, HPV 51/59, HPV 39/68/56/66 all with a corresponding cycle threshold.
QIAsure Methylation Test
The Qiagen QIAsure assay is a multiplex real-time PCR test that amplifies the methylated promoter regions of the tumor suppressor genes, FAM19A4 and has-mir124-2, as well as a methylation-unspecific fragment of the ACTB reference gene. Hypermethylation of the host genes FAM19A4 and has-mir124-2 has been shown to detect high-grade cervical lesions and cancer.
Interventions
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Xpert HPV
The Cepheid Xpert HPV Assay (Xpert HPV) is a qualitative, real-time polymerase chain reaction (PCR) assay for the detection of hrHPV DNA. The assay is formatted in a single-use, Xpert HPV test cartridge and is run on the Cepheid Xpert® System, a multi-analyte, random access, molecular-diagnostic platform ranging in capacity from 1 to 80 test processing modules. Importantly, a single hrHPV DNA test can be completed in one hour, permitting same-day screening and diagnosis (e.g. colposcopy) or treatment (e.g. cryotherapy), reducing the potential for loss to follow-up in lower-resource settings. It uses liquid-based cytologic media and yields five separate results or channels: HPV 16, HPV 18/45, HPV 31/33/35/52/58, HPV 51/59, HPV 39/68/56/66 all with a corresponding cycle threshold.
QIAsure Methylation Test
The Qiagen QIAsure assay is a multiplex real-time PCR test that amplifies the methylated promoter regions of the tumor suppressor genes, FAM19A4 and has-mir124-2, as well as a methylation-unspecific fragment of the ACTB reference gene. Hypermethylation of the host genes FAM19A4 and has-mir124-2 has been shown to detect high-grade cervical lesions and cancer.
Eligibility Criteria
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Inclusion Criteria
* Female.
* Aged 25 to 65.
* Ability to understand and the willingness to sign a written informed consent document by the participant or by the legal representative(s) of the participant.
Exclusion Criteria
* Have undergone cervical cancer screening in the last 6 months.
* Have undergone cervical HSIL treatment in the past year.
* Have a history of hysterectomy with removal of the cervix.
* Have never had sexual intercourse (oral or genital or anal).
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including opportunistic infections of Acquired Immunodeficiency Syndrome-AIDS and/or genitourinary infections), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study due to the lack of safety data of performing colposcopy during pregnancy.
* Any other medical condition or social situation that would put the participant, the study staff, or the study outcomes at risk, as determined by the site investigators.
25 Years
65 Years
FEMALE
No
Sponsors
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National Cancer Institute (NCI)
NIH
H. Lee Moffitt Cancer Center and Research Institute
OTHER
University of Sao Paulo
OTHER
Mexican National Institute of Public Health
OTHER_GOV
University of California, San Diego
OTHER
Instituto Nacional de Salud Publica, Mexico
OTHER
Weill Medical College of Cornell University
OTHER
Responsible Party
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Principal Investigators
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Grant Ellsworth, MD, MS
Role: PRINCIPAL_INVESTIGATOR
Weill Medical College of Cornell University
Locations
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University of São Paulo
São Paulo, , Brazil
National Institute of Public Health, Mexico
Cuernavaca, Morelos, Mexico
Countries
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Other Identifiers
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23-02025683
Identifier Type: -
Identifier Source: org_study_id